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Title: HLA class II genes modulate vaccine-induced antibody responses to affect HIV-1 acquisition
Authors: Heather A. Prentice
Georgia D. Tomaras
Daniel E. Geraghty
Richard Apps
Youyi Fong
Philip K. Ehrenberg
Morgane Rolland
Gustavo H. Kijak
Shelly J. Krebs
Wyatt Nelson
Allan DeCamp
Xiaoying Shen
Nicole L. Yates
Susan Zolla-Pazner
Sorachai Nitayaphan
Supachai Rerks-Ngarm
Jaranit Kaewkungwal
Punnee Pitisuttithum
Guido Ferrari
M. Juliana McElrath
David C. Montefiori
Robert T. Bailer
Richard A. Koup
Robert J. O'Connell
Merlin L. Robb
Nelson L. Michael
Peter B. Gilbert
Jerome H. Kim
Rasmi Thomas
Walter Reed Army Institute of Research
Duke University School of Medicine
Fred Hutchinson Cancer Research Center
Leidos Inc.
NYU School of Medicine
Armed Forces Research Institute of Medical Sciences, Thailand
Thailand Ministry of Public Health
Mahidol University
National Institute of Allergy and Infectious Diseases
Inova Fairfax Medical Campus
Keywords: Medicine
Issue Date: 15-Jul-2015
Citation: Science Translational Medicine. Vol.7, No.296 (2015)
Abstract: © 2015, American Association for the Advancement of Science. All rights reserved. In the RV144 vaccine trial, two antibody responses were found to correlate with HIV-1 acquisition. Because human leukocyte antigen (HLA) class II-restricted CD4+T cells are involved in antibody production, we tested whether HLA class II genotypes affected HIV-1-specific antibody levels and HIV-1 acquisition in 760 individuals. Indeed, antibody responses correlated with acquisition only in the presence of single host HLA alleles. Envelope (Env)-specific immunoglobulin A (IgA) antibodies were associated with increased risk of acquisition specifically in individuals with DQB1∗06. IgG antibody responses to Env amino acid positions 120 to 204 were higher and were associated with decreased risk of acquisition and increased vaccine efficacy only in the presence of DPB1∗13. Screening IgG responses to overlapping peptides spanning Env 120-204 and viral sequence analysis of infected individuals defined differences in vaccine response that were associated with the presence of DPB1∗13 and could be responsible for the protection observed. Overall, the underlying genetic findings indicate that HLA class II modulated the quantity, quality, and efficacy of antibody responses in the RV144 trial.
ISSN: 19466242
Appears in Collections:Scopus 2011-2015

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